crossing96/oncoscreening huggingface dataset:
The impact of routine frozen section analysis during nephroureterectomy or segmental ureterectomy for urothelial carcinoma on final surgical margin status and long-term oncologic outcome.	OBJECTIVE: The utility of intraoperative frozen section analysis (FSA) at the surgical margins (SMs) in patients with upper urinary tract cancer has not been established. We herein assessed the clinical significance of routine FSA of ureteral SMs during nephroureterectomy (NU) or segmental ureterectomy (SU). MATERIALS AND METHODS: A retrospective review of our Surgical Pathology database identified consecutive patients undergoing NU (n=246) or SU (n=42) for urothelial carcinoma from 2004 to 2018. FSA (n=54) was correlated with the diagnosis of frozen section controls, the status of final SMs, and the prognosis of patients. RESULTS: During NU, FSA was performed in 19 (7.7%) patients and was significantly more often requested in cases with ureteral tumor (13.1%) than in those with renal pelvis/calyx tumor (3.5%). Final SMs at the distal ureter/bladder cuff were positive only in non-FSA cases in the entire NU cohort (8.4%; P=0.375) or those with tumor at the lower ureter (57.6%; P=0.046), but not in any of FSA patients (0%). During SU, FSA was performed in 35 (83.3%) cases, including 19 at either proximal or distal SM and 16 at both SMs (SU-FSA2). Final positive SMs were significantly more often detected in non-FSA patients (42.9%) than in all FSA (8.6%; P=0.048) or SU-FSA2 (0%; P=0.020) patients. Overall, FSAs were reported as positive or high-grade carcinoma (n=7), atypical or dysplasia (n=13), and negative (n=34), and all these diagnoses were confirmed accurate on the frozen section controls, except one with a revision from atypical to carcinoma in situ. Meanwhile, 16 (80.0%) of 20 cases with initial positive/atypical FSA achieved negative conversion by excision of additional tissue. Kaplan-Meier analysis revealed that SU-FSA did not significantly reduce the risk of tumor recurrence in the bladder, disease progression, or cancer-specific mortality. Nonetheless, NU-FSA was strongly associated with reduced progression-free (P=0.023) and cancer-specific (P=0.007) survival rates, compared with non-FSA, which may imply a selection bias (e.g., FSA for clinically more aggressive tumors). CONCLUSIONS: Performing FSA during NU for lower ureteral tumor, as well as during SU, significantly reduced the risk of positive SMs. However, routine FSA for upper urinary tract cancer failed to considerably improve long-term oncologic outcome.	bladder
Short-course treatment after complete response to pembrolizumab in metastatic urothelial bladder cancer: a case series.	Background: The optimal duration of treatment for metastatic patients who achieve a complete response with immune checkpoint inhibitors is unknown. Methods: The outcome for six metastatic bladder cancer patients who received short course of pembrolizumab is reported. Results: A median number of seven cycles of pembrolizumab was given. After a median follow-up of 38 months, progressive disease was confirmed in three patients. All patients relapsed in lymph nodes and underwent pembrolizumab rechallenge: one achieved a complete response, another a partial response. Conclusion: Our case series paves the way for discontinuation of pembrolizumab in patients who achieve a complete response since three out of six patients remain free of disease after 3-year follow-up. Prospective studies are required to confirm our results.	bladder
Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence.	BACKGROUND AND OBJECTIVE: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. METHODS: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. RESULTS: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). CONCLUSIONS: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar.	bladder
The efficacy and safety outcomes of lower dose BCG compared to intravesical chemotherapy in non-muscle-invasive bladder cancer: A network meta-analysis.	This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.	bladder
Metastasis to the penis from a bladder carcinoma invading only the lamina propria: case report and description of the morphological aspects.	INTRODUCTION: Data shows that bladder cancer (BC) takes the seventh place as the most commonly diagnosed when it comes to the male population. Whereas when both genders considered, it moves down the tenth place. Although 75% of patients with BC present with the disease confined to the mucosa or submucosa, rarely secondary metastasis to the penis occurs. CASE PRESENTATION: A 73-year-old male was referred for gross hematuria in May 2018. A cystoscopy was performed detecting a bladder tumor. The resection of the tumor revealed an invasive high-grade (HG) papillary transitional carcinoma of the bladder with nest variants and lamina propria invasion. The histological examination of the second-look resection disclosed the same tumor characteristics. The patient was scheduled for bacillus Calmette-Guérin (BCG) instillations. Meanwhile, he was diagnosed and treated for a primitive lung acinar adenocarcinoma. Seven months after the first diagnosis, the patient progressed to cT4 at the level of the bladder. He underwent four cycles of Methotrexate, Vinblastine, Doxorubicin (Adriamycin) and Cisplatin (MVAC) chemotherapy followed by a cystoprostatectomy. The histological result was fibrosis and ypT0pN0 classification. Due to pain and solid mass in the penis, a total penectomy was performed and the histological result showed a transitional carcinoma suggesting a metastasis of the urothelial carcinoma of the bladder. Three months following the penectomy, a positron emission tomography∕computed tomography (PET∕CT) scan results showed multiple metastases and positive lymph nodes. Hence, Pembrolizumab treatment was started, providing very good clinical and radiological evolution. At the time of publishing, the patient is alive, and the radiological exams show stability of the disease. CONCLUSIONS: The detailed descriptions of all histological variants of carcinoma of the bladder in the specimen has great importance and significant impact on the management of the disease.	bladder
Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer.	Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.	bladder
Uncovering the potential functions of lymph node metastasis-associated aberrant methylation differentially expressed genes and their association with the immune infiltration and prognosis in bladder urothelial carcinoma.	BACKGROUND: Bladder urothelial carcinoma (BLCA) is a malignant tumor of the urinary system. This study aimed to explore the potential role of lymph node metastasis-associated aberrant methylation differentially expressed genes (DEGs) in BLCA. METHODS: CHAMP and limma packages were used to identify lymph node metastasis-associated aberrant methylation DEGs. Univariate Cox analysis and Lasso analysis were performed to identify the signature genes, and multivariate Cox analysis was used to construct the risk score. Subsequently, the molecular characteristics of the signature genes and the relationship between risk score and prognosis, clinical characteristics and immune cell infiltration were analyzed. The signature gene AKAP7 was selected for functional verification. RESULTS: A novel risk score model was constructed based on 12 signature genes. The risk score had a good ability to predict overall survival (OS). The nomogram constructed based on age, N stage and risk score had a higher value in predicting the prognosis of patients. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA. Immunohistochemistry showed that AKAP7 may be associated with the occurrence, clinical stages and grades, and lymph node metastasis of BLCA. In vitro cell experiments showed that the migration and invasion ability of EJ cells was significantly inhibited after AKAP7 overexpression, while the migration and invasion ability of T24 cells was significantly promoted after AKAP7 knockdown. CONCLUSION: The risk score model based on lymph node metastasis-associated aberrant methylation DEGs has a good ability to predict OS and is an independent prognostic factor for BLCA. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. This implicates aberrant methylation modifications as an important factor contributing to the heterogeneity and complexity of individual tumor microenvironments. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA, which contributed to the exploration of the pathological mechanism of BLCA. In addition, immunohistochemistry showed that AKAP7 may be associated with the occurrence, progression and lymph node metastasis of BLCA. In vitro cell experiments showed that AKAP7 could also inhibit the migration and invasion of cancer cells.	bladder
Prophylactic Mesh Placement With Ileal Conduit: A Cost-effectiveness Analysis.	OBJECTIVE: To determine the cost-effectiveness of mesh placement in patients undergoing ileal conduit urinary diversion for bladder cancer. Long-term studies have shown that parastomal hernias (PSH) occur in more than half of all stomas. Mesh prophylaxis has been shown to reduce PSH after end-colostomy and ileal conduits. However, no cost-effectiveness studies on mesh prophylaxis have been performed for this population. METHODS: We created a Markov model incorporating the costs and effectiveness of mesh prophylaxis for patients undergoing radical cystectomy and ileal conduit construction. Costs were obtained from the literature and adjusted to 2022 US dollars. Effectiveness was measured in quality-adjusted life years (QALY). 1- and 2-way sensitivity analyses were performed to test the robustness of our model. RESULTS: In stage I-IV bladder cancer, prophylactic mesh placement was costlier, but more effective in providing quality of life compared with no mesh placement at index surgery. Average incremental cost between the 2 strategies across all stages was an additional $897 when mesh was utilized. Incremental effectiveness averaged 0.49 additional QALY across all stages. This resulted in an incremental cost-effectiveness ratio of $2114.71/QALY. Sensitivity analyses indicated that benefit of mesh placement was sensitive to the probability of mesh infection. CONCLUSION: In patients undergoing ileal conduit urinary diversion for bladder cancer, mesh prophylaxis at the time of radical cystectomy is an overall cost-effective strategy in preventing PSH for patients presenting with all stages of bladder cancer.	bladder
Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma.	The antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for human epidermal growth factor receptor 2 (HER2/ERBB2)-positive breast cancer. We aimed to study tumor HER2 expression and its effects on T-DM1 responses in patients with HER2-positive urothelial bladder cancer (UBC) or pancreatic cancer (PC)/cholangiocarcinoma (CC). In the phase II KAMELEON study (NCT02999672), HER2 status was centrally assessed by immunohistochemistry, with positivity defined as non-focal homogeneous or heterogeneous overexpression of HER2 in ≥30% of stained cells. We also performed exploratory biomarker analyses (e.g., gene-protein assay) on tissue samples collected from study participants and consenting patients who failed screening. Of the 284 patients successfully screened for HER2 status (UBC, n = 69; PC/CC, n = 215), 13 with UBC, four with PC, and three with CC fulfilled eligibility criteria. Due to recruitment difficulty, the sponsor terminated KAMELEON prematurely. Of the five responders in the UBC cohort (overall response rate, 38.5%), HER2 expression was heterogeneous in two and homogeneous in three. The one responder in the PC/CC cohort had PC, and the tumor displayed homogeneous expression. In the biomarker-evaluable population, composed of screen-failed and enrolled patients, 24.3% (9/37), 1.5% (1/66), and 8.2% (4/49) of those with UBC, PC, or CC, respectively, had HER2-positive tumors. In a gene-protein assay combining in situ hybridization with immunohistochemistry, greater HER2 homogeneity was associated with increased ERBB2 amplification ratio. In conclusion, KAMELEON showed that some patients with HER2-positive UBC or PC can respond to T-DM1 and provided insight into the prevalence of HER2 positivity and expression patterns in three non-breast tumor types.	bladder
Hypermethylated ITGA8 Facilitate Bladder Cancer Cell Proliferation and Metastasis.	DNA methylation plays a vital role during the development of tumorigenesis. The purpose of this study is to identify candidate DNA methylation drivers during progression of bladder cancer (BLCA). The methylation spectrum in bladder cancer tissues was detected by CHARM analysis, and methylated ITGA8 was selected for further study due to its low expression. Methylation levels in BLCA tissues and cells were detected with methylated-specific PCR (MSP), while mRNA expression and methylation of ITGA8 were detected by qRT-PCR and MSP. After treatment with 5-Aza-dC (DNA methylation inhibitor), the proliferation, migration, and invasion abilities of BLCA cells were determined by MTT, wound healing, and transwell assays, respectively. Flow cytometric analysis was performed to evaluate any variance in the cell cycle. In addition, the effect of demethylated ITGA8 on BLCA tumor growth was verified with an in vivo xenograft tumor model. Based on the methylation profiling of BLCA, ITGA8 was identified to be hypermethylated. ITGA8 methylation levels in BLCA tissues and cells were upregulated, and 5-Aza-dC significantly suppressed ITGA8 methylation levels and increased ITGA8 mRNA expression. Furthermore, after treatment with 5-Aza-dC, the propagation, migration, and invasiveness of the cancer cells were inhibited, and more cancer cells were arrested at the G0/G1 phase. In vivo assays further demonstrated that 5-Aza-dC could impede BLCA tumor growth by repressing methylation levels of ITGA8 and increasing ITGA8 mRNA expression. Hypermethylated ITGA8 facilitated BLCA progression, and 5-Aza-dC treatment inhibited BLCA cell propagation and metastasis by decreasing methylation levels of ITGA8 and inducing cell cycle arrest.	bladder
The correlation of EMT and p53 immunohistochemical markers with cisplatin resistance in muscle invasive bladder cancer patients: A single-centred study.	INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients. MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53. RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case. CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.	bladder
Apoptosis related genes mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide immunotherapy in bladder cancer.	"Apoptosis has been discovered as a mechanism of cell death. The purpose of this study is to identify the diagnostic signature factors related to bladder cancer (BLCA) through apoptosis related genes (ARGs). Clinicopathological parameters and transcriptomics data of 1,440 BLCA patients were obtained from 7 datasets (GSE13507, GSE31684, GSE32548, GSE32894, GSE48075, TCGA-BLCA, and IMvigor210). We first identified prognosis-related ARGs in BLCA and used them to construct two ARGs molecular subtypes by using consensus clustering algorithm. By using principal component analysis algorithms, a ARGscore was constructed to quantify the index of individualized patient. High ARGscore correlated with progressive malignancy and poor outcomes in BLCA patients. High ARGscore was associated with higher immune cell, higher estimate scores, higher stromal scores, higher immune scores, higher immune checkpoint, and lower tumor purity, which was consistent with the ""immunity tidal model theory"". Preclinically, BLCA immunotherapy cohorts confirmed patients with low ARGscore demonstrated significant therapeutic advantages and clinical benefits. These findings contribute to our understanding of ARGs and immunotherapy in BLCA. The ARGscore is a potentially useful tool to predict the prognosis and immunotherapy in BLCA."	bladder